My interest in research began as an undergraduate at the University of Arizona (U of A). Since that time I have developed as an independent scientist in the field of pain. Several milestones are noteworthy including the establishment of my laboratory, recruitment of students and a postdoctoral fellow, receiving my first 5 year R01 NIH-NIDA sponsored grant, invitations to speak at national/international meetings and in academic settings, forging new collaborations and continuous publications in peer reviewed journals. These accomplishments have offered a taste of a career in which I hunger for, however my appointment in the Department of Pharmacology came with a significant teaching commitment that, although important tends to abate my time for basic research. If I were to receive this Career Development Award, I would pursue specific research objectives including;1) Continue to strengthen my primary research program;2) Develop a new/extended hypothesis for a renewal of the current NIH-R01;3) Publish;4) Present my data at national/ international meetings;5) Collaborate with the group of pain-neuroscientist/ pharmacologists/chemists here at the U of A. My research career goal is to establish an interdisciplinary research program aimed at understanding the mechanisms that drive the activation of supraspinal descending pain facilitatory pathways in the presence of sustained opioids. The ultimate goal of these studies is to understand the neurobiological consequences of sustained opioid administration and to determine the role of these adaptations. This proposal hypothesizes that morphine enhances cholecystokinin (CCK) release in the RVM which then promotes opioid-induced pain and antinociceptive "tolerance". The studies offer new insight into physiological mechanisms of opioid tolerance and strategies which might be employed to prevent opioid-induced pain and antinociceptive tolerance which may allow for the development of novel pain relieving compounds. The U of A has earned recognition as a top Research One University ranked 13th among public universities. The U of A has in place the infrastructure needed to support and oversee research activities including several core research laboratories, interdisciplinary academic programs and large multi-disciplinary center programs. These facilities were put into place to support and promote interdisciplinary collaborations which initiate new research and educational programs of high priority to the scientific community. I have adequate space, equipment, the ability to recruit graduate students from multiple programs, and have access to numerous shared resources. In summary, the U of A and the Department of Pharmacology provide an outstanding environment to promote science and foster career development.